A resolution of the protein folding problem would allow an understanding of how ordered linear sequences of amino acid residues carry the information required to regulate folding to a compact well-defined native protein geometry that carries with it the capacity to perform useful biological tasks such as catalysis, molecular recognition, and transformation of chemical to mechanical work. Predictive, rational design of man-made proteins that perform useful tasks would be one consequence; a deep understanding of a central problem in structural biology would be another. Many workers in the field of protein folding subscribe to a model in which the first event in the folding process is the formation along the peptide backbone of isolated groups of secondary structure, such as Beta-sheets and of helices. Coiling of these preformed groups then leads to formation of the compact protein. A basic understanding of the rules for formation of secondary structure has been hitherto difficult to achieve, owing to the absence of good simple models that allow observation in solution of secondary structure formation as an isolated event. The long term objective of this project is the preparation and study of synthetically 'chimeric' large peptides and small proteins in which normal sequences of amino acids are linked to rigid chemical spacers that can confer local secondary structure on linked polypeptides through conformational signals such as hydrogen bonds. From the study of these chimeric molecules it is expected that predictive rules for the formation of secondary structure and for the packing of formed elements of secondary structure can be developed as the result of direct observation. In the process of analyzing the properties of these species, current models and concepts concerning the essential elements in the folding process will be tested. The specific aim of this project is construction of template-linked peptides that assume stable, predictable conformations in aqueous solution that can be analyzed by modern high-field NMR spectroscopy.